雌激素干预昼夜节律变化与皮肤老化

雌激素影响皮肤组织的发育和生理功能，女性皮肤会随着体内雌激素水平的变化而逐渐老化，在雌激素水平发生急性或慢性变化的时期，包括围产期、妊娠期、更年期和生殖周期，昼夜节律紊乱的发生率随之增加。植物雌激素既能实现对皮肤的特定雌激素样作用，显著延缓皮肤衰老，又能起到昼夜节律调节剂的作用，预防或治疗昼夜节律相关疾病。本文阐述了雌激素与昼夜节律系统的相互作用关系，及其水平变化对皮肤老化的影响，并为使用植物雌激素延缓皮肤衰老和调节昼夜节律提供理论支持。     

雌激素对皮肤和毛发生物学作用的研究进展

雌激素在抗皮肤老化、加速皮肤损伤修复、促进毛发生长、抑制皮脂腺分泌等方面均发挥重要作用。已经发现的雌激素受体有两种，即雌激素受体-α、-β。雌激素受体-α、-β是由不同的基因编码的两种蛋白质，具有高度的同源性。雌激素受体在皮肤中的精确定位使人们对雌激素在皮肤中的生物学作用的研究更为深入、广泛。     

毛发疾病

941577 正常人体多毛部位皮肤雌激素受体的比较研究/周光平…//临床皮肤科杂志。-1994,23(2).-71～73 对10例毛发分布正常的健康男性头皮、眉部、胡须、腋部、阴部皮肤应用直接荧光组织化学法检测雌激素受体(ER)。结果:表皮细胞、毛囊外毛根鞘及少数内毛根鞘、皮脂腺、大小汗腺、立毛肌、真皮纤维母细胞、毛     

敬老院老年人皮肤浅部真菌感染调查

目的了解敬老院老年人皮肤浅部真菌感染情况，并进行菌种分析，探讨易感因素，帮助敬老院老年人做好预防和健康管理。方法对黑龙江省牡丹江市一所敬老院398名老年人进行问卷调查及皮肤科检查，并进行皮损真菌镜检、培养及菌种分析。结果敬老院老年人皮肤浅部真菌感染占首位（除脂溢性角化病、老年皮肤瘙痒症及皮肤退行性改变所致皮肤病），其中以足癣和甲真菌病为主。生活不能自理老年人皮肤浅部真菌感染发病率高于生活能够自理老年人；并发糖尿病、脑血管病、慢性支气管炎和肺心病的老年人，皮肤浅部真菌感染发病率高于敬老院老年人皮肤浅部真菌感染发病率。致病菌种以念珠菌感染为主（44．78％），其次为红色毛癣菌（34．33％）。结论老年人生活自理能力下降，并发糖尿病、脑血管病及慢性支气管炎和肺心病是真菌感染的易发因素。     

雌激素对皮肤和毛发生物学作用的研究进展

雌激素在抗皮肤老化、加速皮肤损伤修复、促进毛发生长、抑制皮脂腺分泌等方面均发挥重要作用。已经发现的雌激素受体有两种,即雌激素受体-α、-β。雌激素受体-α、-β是由不同的基因编码的两种蛋白质,具有高度的同源性。雌激素受体在皮肤中的精确定位使人们对雌激素在皮肤中的生物学作用的研究更为深入、广泛。     

局部外用雌激素治疗皮肤老化

皮肤老化症状随着更年期的到来而出现,提示雌激素水平下降是否是内源性皮肤老化的重要原因。几年前有人以雌激素外用治疗外阴、阴道萎缩取得一定的疗效。最近,作者用0.01％雌二醇(E2)和0.3％雌三醇对照治疗了59例更年期妇女的皮肤老化,研究雌激素与皮肤老化的关系。具体方法是:选择59例合适患者,分成两组,分别用0.01％E2和0.3％雌三醇外用面、颈部皮肤,每天1g,坚持治疗6个月,观察:①临床表现,如皱褶、皮肤弹性、毛孔     

雌激素与皮肤老化的研究进展

雌激素对皮肤有重要的影响,其相对减少可加重皮肤的内源性和外源性衰老.一定量的雌激素能通过增加皮肤的厚度、水分和弹性,减少皮肤皱纹,防止皮肤老化.因此雌激素是治疗皮肤老化的有效方法之一.局部外用雌激素治疗皮肤老化的疗效与安全性已经肯定,而雌激素替代疗法治疗皮肤老化的疗效还有待进一步研究证实.     

皮肤肿瘤中的雌激素受体及皮肤恶性黑素瘤中雌激素和孕激素受体及C－erbB2癌基因的表达

通过对８个病种的２１例皮肤恶性肿瘤进行的雌激素受体的免疫组化标记（ＡＢＣ法），发现有２例皮肤恶性黑素瘤呈阳性表达。在１５例皮肤恶性黑素瘤中进行的免疫组化染色中（ＬＳＡＢ），雌激素受体阳性７例、孕激素受体阳性３例、Ｃ－ｅｒｂＢ２癌基因阳性７例。作者认为通过进一步研究有望获得恶性黑素瘤激素治疗和预后观察的生物学依据     

雌激素受体在女性面部皮肤的表达

用免疫组化方法检测雌激素受体在女性面部皮肤中的表达.探讨皮肤形态特点和老化与雌激素的关系.显示雌激素受体的两种亚型(ERα,ERβ)在皮肤均有表达,其中ERα只表达在皮脂腺细胞核中;ERβ在皮肤表达广泛,是皮肤的主要雌激素受体,真皮成纤维细胞、表皮基底细胞、皮脂腺细胞、毛囊外毛根鞘细胞、汗管内皮细胞均有ERβ表达.皮肤是雌激素重要的靶器官,可从各个方面影响皮肤的结构和功能.毛发的生长和脱落,皮脂分泌、皮肤老化进程都与雌激素有关.     

皮肤肿瘤中的雌激素受体及皮肤恶性黑素瘤中雌激素和孕激素…

通过对８个病种的２１例皮肤恶性肿瘤进行的雌激素受体的免疫组化标记，发现有２例皮肤恶性黑一素瘤呈阳性表达。在１５例皮肤恶性黑素瘤中进行的免疫组化染色中，雌激素受体阳性７例，孕激素受体阳性３例，Ｃ－ｅｒｂＢ２癌基因阳性７例，作者认为通过进一步研究有望获得恶性黑素瘤激素治疗和预后观察的生物学依据。     

Expression of estrogen-related receptor gamma (ERRgamma) in human skin

Skin is a non-classical target for estrogens. Despite evidence showing that estrogen receptors (ER) are expressed in skin, there are still extensive gaps in our understanding of how estrogens exert their action in non-reproductive tissues. Estrogen-related receptor gamma (ERRgamma), an orphan member of the nuclear receptor superfamily, shows a strong sequence homology with estrogen receptor alpha but it does not bind estradiol. Here, for the first time, we demonstrate the expression of ERRgamma in adult human skin. ERRgamma mRNA was detected in the keratinocytes and fibroblasts of 8 female donor skins using RT-PCR. The presence of the protein was confirmed using immunohistochemistry on 11 adult human skins and Western Blotting on monolayer-cultures of fibroblasts and keratinocytes from respectively 4 and 2 donors. This study shows that ERRgamma is expressed in human skin and could intervene in a potentially new estrogen signaling pathway in the skin.     

Marked improvement induced in photoaged skin of hairless mouse by ER36009, a novel RARgamma-specific retinoid, but not by ER35794, an RXR-selective agonist

BACKGROUND: Photoaging (premature skin aging) results largely from repeated exposure of the skin to ultraviolet (UV) radiation from the sun. Topical all-trans retinoic acid (RA), the only agent that has been approved for the treatment of photoaging, has been shown to reverse this process. In this study, we evaluated the pharmacologic effects of novel synthetic retinoids, ER36009 and ER35794, on murine wrinkles induced by UVB. ER36009 is a specific agonist of retinoic acid receptor (RAR)gamma, the most abundant RAR subtype in the skin, while ER35794 is a potent retinoid X receptor (RXR)-selective agonist. METHOD: After a 10-week exposure to escalating doses of UVB irradiation, the animals were treated three times per week with ER36009 (0.0001%, 0.00025%, 0.0005%), ER35794 (0.025%, 0.05%, 0.1%), RA (0.05%) or acetone (control) for 3 weeks. RESULTS: ER36009 exerted a dose-dependent wrinkle-effacing effect, and 0.0005% ER36009-treated skin was significantly different from the control. ER36009 also significantly and dose-dependently increased both epidermal thickness and the area of the dermal repair zone defined by newly synthesized collagen. The effect of 0.0005% ER36009 on photodamaged skin was superior to that of 0.05% RA. In contrast, ER35794 was inactive in this model, though this compound exhibited lower local toxicity than other retinoids. CONCLUSIONS: These data indicate that RARgamma, but not RXR, plays an important role in the improvement of the signs of photoaging, and so a specific RARgamma agonist might be superior to an RAR pan-agonist for clinical treatment. We conclude that ER36009 is a candidate for a potent anti-skin-aging agent.     

Estrogen receptor status in malignant melanoma

Estrogen receptor (ER) positivity demonstrated in malignant melanomas by histochemical and biochemical assays suggested the possibility of hormonal management and improved prognosis as for breast carcinoma patients. We studied the ER status of 5 primary and 28 metastatic malignant melanomas with a commercial immunohistochemical kit (ER-ICA monoclonal), that utilizes monoclonal anti-ER and a peroxidase-antiperoxidase technique, and by a histochemical method using fluorescein-conjugated estradiol (Fluoro-Cep Estrogen assay), on frozen sections. In addition, we conducted a biochemical assay [dextran-coated charcoal cytosolic assay (DCC)] in 16 cases. All 33 cases were ER negative by ER-ICA and Fluoro-Cep: 11 biochemical assays were negative (less than 3 fmol ER/mg protein), four were in the borderline range (3 to 10 fmol ER/mg protein), and one was positive (greater than 10 fmol ER/mg protein) at 11 fmol. The melanomas in 97% of the cases we studied were ER negative by two or three different assays. Low-level estrogen binding of MM tissues may be the result of interactions other than with Type I true ER. The low frequency of ER positivity of malignant melanomas appears to preclude the clinical use of ER status as an indicator for response to hormonal manipulation in patients with malignant melanoma.     

苯甲酸雌二醇及UVA辐照对体外培养的人皮肤成纤维细胞胶原合成的影响

目的探讨苯甲酸雌二醇对体外培养的人成纤维细胞增殖、胶原合成及其对UVA抑制胶原合成的影响。方法在培养的人成纤维细胞中分别加入不同剂量的苯甲酸雌二醇,继续培养48h,用MTT法测定细胞的增殖情况,同时应用RT-PCR方法检测经不同剂量苯甲酸雌二醇及10J/cm²UVA处理后人成纤维细胞Ⅰ、Ⅲ型前胶原mRNA的表达情况。结果MTT法检测结果显示,苯甲酸雌二醇对体外培养的成纤维细胞增殖无明显促进作用。RT-PCR结果提示,苯甲酸雌二醇处理组两型前胶原的表达水平明显上调(P<0.05),而UVA照射后两型前胶原的表达显著下降,苯甲酸雌二醇可在一定水平对抗其作用(P<0.05)。结论苯甲酸雌二醇对体外培养的成纤维细胞Ⅰ、Ⅲ型前胶原的合成有一定的促进作用,并可对抗紫外线抑制胶原合成的作用。     

Human scalp hair: Modulation by various factors and hormones do estrogens inhibit or stimulate—A perplexing perspective

Several journal reports, reviews, and commentaries over the last 20‐25 years have pointed out the controversy attached to 17β‐estradiol's inhibitory or stimulatory influence on hair follicle growth/cycling citing rodent (murine) and human results. While 17β‐estradiol is the most potent sex steroid hormone in the body and has almost equal affinity for estrogen receptor (ER) alpha (α) and beta (β), there appears to be specific ER‐mediated effects on scalp hair follicles/growth, etc. Additionally, the newly discovered G protein‐coupled estrogen receptor (GPR30 or GPER) and the orphan receptor, estrogen‐related receptor (ERR) gamma (γ), in skin and other tissue sites have potential impacts of how estrogens via these receptors may alter scalp hair characteristics, but this remains to be elucidated. Conversely, the negative impact of the 5α‐reductase enzyme and its steroid product, 5α‐dihydrotestosterone, on scalp hair growth is clear. Less clear is how 17β‐estradiol is stimulatory in some scalp hair studies, but inhibitory in others. This brief summary examines the potential influences of steroidogenesis via aromatase (estrogen biosynthesis) and 5α‐reductase expression, their enzyme activities, and steroid products along with the concepts of how steroid acute regulatory protein (StAR) and estrone sulfate may be involved in the complex hormonal, cellular/molecular signaling cascade of the hair follicle in growth and cycling.     

Oestrogen and progesterone receptor expression in melasma: an immunohistochemical analysis

Background Melasma is a commonly acquired symmetrical hypermelanosis on sun‐exposed areas of the skin. The development of melasma appears to be associated with increased levels of oestrogen, exposure to sunlight and a genetic predisposition. Several in vitro studies have partially clarified the effects of oestrogen and progesterone on melasma. However, oestrogen receptor (ER) and progesterone receptor (PR) expression in melasma‐affected skin has not been investigated to date, except for one case report on ER expression. Objective The purpose of this study was to compare ER and PR expression between hyperpigmented areas and unaffected areas of facial skin in patients with melasma. Methods Biopsies were performed on skin lesions and adjacent‐unaffected facial skin in 33 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana‐Masson, and antibodies to NKI/beteb, ERα, β and PR. Results The immunohistochemical expression of ERβ showed an increasing tendency in epidermal lesions without statistical significance. Expression of PR was significantly increased in the epidermal lesions compared with unaffected skin on the computer‐assisted image analysis. Interestingly, there was increased ERβ expression in the dermal lesions especially around small blood vessels and fibroblast‐like cells compared with unaffected dermis on the semi‐quantitative analysis. However, there was no significant difference in the expression of PR between the dermal lesions and unaffected dermis. Conclusion The results of this study may provide useful information for further investigation into the pathogenesis and therapeutic approaches for treating melasma in relation to hormonal factors. The role of ER in the dermis in association with dermal environment such as blood vessels and fibroblasts remains to be further clarified.     

Steroid hormone receptors in normal skin

Hormonal influences modulate various skin functions. Despite of skin manifestations indicative of increased androgenic influence, many cases show normal hormone serum levels. The target organ sensitivity of skin may be figured out by hormone receptor analysis. Our study presents data from 60 volunteer patients regarding estrogen (ER), androgen (AR), and gestagen (PgR) receptor analysis in normal skin. The highest percentages of AR and ER were found in the face of male and female patients followed by the lower extremities. Equal AR levels in both sexes indicate equal androgenic stimulability at the cellular level in both sexes. ER levels were higher in female than in male patients. PgR was negative in 14 cases. Nor could we prove any receptors in the youngest group of patients. Our results correspond with the clinical observation of different hormonal stimulability in various skin regions.     

Control of androgen receptor expression in human keratinocytes and in a reconstituted human epidermis model with selective antisense oligonucleotides

Clinical evidence of correlations between menopause and endogenous skin aging gave input to various studies investigating the relevance of estrogens for skin functions that are associated with skin aging and their possible therapeutic effects. Skin thickness and bone density are significantly decreased already six months after menopause and are increased after the same period of hormone replacement (HRT). Fibroblast and keratinocyte function is stimulated by estrogen application, and among other effects significant increases of collagen fibres have been demonstrated six months after the onset of HRT ( 1 ). Topical use of estrogen compounds was found to diminish skin aging symptoms. The effects of conjugated estrogens (0,625% Premarin) were studied in 60 postmenopausal women ( 2 ). In another study the effects of estradiol 0,01% and estriol 0,3% were compared ( 3 ). Both studies documented significant reductions of wrinkles without any systemic side effects of the treatments. Recently significant increases of epidermal thickness during estradiol have been described ( 4 ). For cosmetic purposes phytoestrogens seem a promising alternative to the medical treatment. Isoflavone containing cosmetical creams were shown to improve skin dryness and wrinkles ( 5 ). In various studies mainly beneficial effects of systemic HRT on skin aging parameters have been documented. Although skin aging is certainly no indication for systemic hormone supplementation the beneficial action of such treatment on aging symptoms of the skin are a positive side aspect of such treatment.